2008
DOI: 10.1158/1078-0432.ccr-07-5235
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Impaired Tamoxifen Metabolism Reduces Survival in Familial Breast Cancer Patients

Abstract: Purpose: Tamoxifen has been the mainstay adjuvant hormonal treatment for breast cancer for many years. Conversion of tamoxifen to its active metabolite, endoxifen, is reduced by low activity of the cytochrome P450 enzyme, CYP2D6.We examined the effect of reduced CYP2D6 activity on the response to tamoxifen in patients with familial early-onset breast cancer. Experimental Design: We conducted a case note review and genotyping for the CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*41 alleles in 115 patients (47 BRCA1,… Show more

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Cited by 106 publications
(112 citation statements)
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“…The 115 enrolled patients were genotyped for the CYP2D6 *wt, *3, *4, *5 and *41 alleles. Poor metabolizers showed a significantly worse overall survival, a condition that was also observed in the subset analysis considering only CYP2D6*4, especially in BRCA2 carriers [16] . Karle et al [17] analysed the effect of the CYP2D6 genotyping in a palliative setting, enrolling 88 patients with ER positive advanced breast cancer.…”
Section: Researchsupporting
confidence: 71%
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“…The 115 enrolled patients were genotyped for the CYP2D6 *wt, *3, *4, *5 and *41 alleles. Poor metabolizers showed a significantly worse overall survival, a condition that was also observed in the subset analysis considering only CYP2D6*4, especially in BRCA2 carriers [16] . Karle et al [17] analysed the effect of the CYP2D6 genotyping in a palliative setting, enrolling 88 patients with ER positive advanced breast cancer.…”
Section: Researchsupporting
confidence: 71%
“…In five of them the investigation focused exclusively on allele*4, while in the study of Newmann et al [16] performed in patients with familiar breast cancer, a subanalysis for *4 alone has also been performed [7,8,11,13,15] . In six other, the analysis included a larger pool of intermediate/poor metabolizers based on a combined basis of common non-functional alleles, including allele*4 [6,7,9,11,14,16] . All of them were unique regarding the worse clinical course of ER+ breast cancer under tamoxifen therapy in non-extensive metabolizers.…”
Section: Discussionmentioning
confidence: 99%
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“…Reasons for this inconsistency in previous studies include differences in SSRI inhibition ability, genomic differences, differences in data collection, limited information on tamoxifen compliance, and small sample size [274]. Research on genotype and concomitant antidepressant use is also limited by small sample size [280][281][282], with sample sizes in some studies ranging from n=4 to n=13, too small to draw any conclusion [281,282]. More research must be conducted to determine if this interaction truly exists.…”
Section: Antidepressant Usementioning
confidence: 99%